This proposal is to request support for a Keystone Symposia meeting entitled "Innate, Adaptive and Regulatory Immune Responses to Intestinal Microbiota", organized by R. Balfour Sartor, Lloyd F. Mayer, Charles O. Elson and Scott Plevy, which will be held in Taos, New Mexico from January 13 18, 2009. Mucosal defenses and immunoregulation have a key role in maintaining homeostasis in response to the commensal microbial environment in the distal intestine. This meeting will discuss the latest information regarding the induction of protective and effector innate and adapter immune responses to the commensal intestinal microbiota that lead to mucosal homeostasis vs. chronic immune mediated intestinal inflammation. We highlight the protective role of innate mucosal immune responses induced by ligation of TLR and NOD 2/CARD 15 to activate NF-:B and other signaling pathways. Mechanisms of bacterial killing by epithelial and phagocytic cells are explored. The interface of antigen presenting cell/T cell activation leading to effector and regulatory T cell function in the intestine is examined with a particular emphasis on bacterial antigen-specific responses. Finally, biomedical applications of these basic research observations are explored. These basic and translational studies have direct implications for understanding the pathophysiology of chronic intestinal inflammation such as Crohn's disease, ulcerative colitis and pouchitis, and emphasize innate and adaptive immunoregulatory mechanisms that mediate mucosal homeostasis in a hostile environment. Major unresolved issues in mucosal immunology are as follows: (1) understanding how epithelial cells coexist with commensal intestinal bacteria, yet recognize the pathogenic organisms;(2) understanding how effector mechanisms in innate immune cells and T cells are appropriately downregulated;and (3) how understanding of basic immune regulation and inflammation can lead to the development of novel therapeutic agents for chronic inflammatory bowel diseases. This meeting will present state of the art lectures on the most recent research on innate, adaptive and regulatory immune responses to commensal bacteria and will explore several novel therapeutic approaches derived from recent pathogenic insights. Inflammatory bowel diseases (IBD) affect an estimated 1.5 million people in the United States, with the highest incidence in adolescents and young adults. These disorders are chronic, can be debilitating, and have no medical cure. This meeting explores the most recent research on innate, adaptive and regulatory immune responses to commensal bacteria, promotes interdisciplinary research interactions and explores several novel therapeutic approaches derived from recent pathogenic insights.